CNT@TiO2 nanohybrids for high-performance anode of lithium-ion batteries.
This work describes a potential anode material for lithium-ion batteries (LIBs), namely, anatase TiO2 nanoparticle-decorated carbon nanotubes (CNTs@TiO2). The electrochemical properties of CNTs@TiO2 were thoroughly investigated using various electrochemical techniques, including cyclic voltammetry, electrochemical impedance spectroscopy, galvanostatic cycling, and rate experiments. It was revealed that compared with pure TiO2 nanoparticles and CNTs alone, the CNT@TiO2 nanohybrids offered superior rate capability and achieved better cycling performance when used as anodes of LIBs. The CNT@TiO2 nanohybrids exhibited a cycling stability with high reversible capacity of about 190 mAh g-1 after 120 cycles at a current density of 100 mA g-1 and an excellent rate capability (up to 100 mAh g-1 at a current density of 1,000 mA g-1).


Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer.
Although some retrospective studies have suggested the value of adjuvant therapy, no recommended standard exists in bile duct cancer. The aim of this study was to test the hypothesis that adjuvant gemcitabine chemotherapy would improve survival probability in resected bile duct cancer. This was a randomized phase III trial. Patients with resected bile duct cancer were assigned randomly to gemcitabine and observation groups, which were balanced with respect to lymph node status, residual tumour status and tumour location. Gemcitabine was given intravenously at a dose of 1000 mg/m2 , administered on days 1, 8 and 15 every 4 weeks for six cycles. The primary endpoint was overall survival, and secondary endpoints were relapse-free survival, subgroup analysis and toxicity. Some 225 patients were included (117 gemcitabine, 108 observation). Baseline characteristics were well balanced between the gemcitabine and observation groups. There were no significant differences in overall survival (median 62·3 versus 63·8 months respectively; hazard ratio 1·01, 95 per cent c.i. 0·70 to 1·45; P = 0·964) and relapse-free survival (median 36·0 versus 39·9 months; hazard ratio 0·93, 0·66 to 1·32; P = 0·693). There were no survival differences between the two groups in subsets stratified by lymph node status and margin status. Although haematological toxicity occurred frequently in the gemcitabine group, most toxicities were transient, and grade 3/4 non-haematological toxicity was rare. The survival probability in patients with resected bile duct cancer was not significantly different between the gemcitabine adjuvant chemotherapy group and the observation group. Registration number: UMIN 000000820 (http://www.umin.ac.jp/).


Low dosage oral contraception in women with previous gestational diabetes.
The carbohydrate metabolic status in 10 women with previous non-insulin-dependent diabetes in pregnancy and in 8 control subjects was evaluated prospectively during a 6-month treatment period with an oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel. An oral glucose tolerance test was performed before treatment and after tablet intake for 2 and 6 months. At each test, plasma values of glucose, insulin, and glucagon were measured. Before treatment the non-insulin-dependent diabetic patients demonstrated significantly increased glucose values and decreased insulin values as compared with the values of the control subjects. During treatment they displayed a small but significant rise in plasma insulin values. The glucose tolerance, however, remained unaffected in both groups during the study period. No change in body weight or blood pressure was observed. The results indicate that hormonal contraception of the low dosage type may be administered to women with previously impaired glucose tolerance in pregnancy without any deterioration of the glucose metabolism post partum.


Effect of Yoga on the Motor Proficiency of Children with Autism Spectrum Disorder and the Feasibility of its Inclusion in Special School Environments.
Yoga as a movement-based intervention is increasingly considered to improve the motor skills of children with autism spectrum disorder (ASD). However, there is little evidence of the effect of yoga on their motor skills. The current study aims to explore the effect of group yoga program on motor proficiency of children with ASD and feasibility of its inclusion in special schools. Forty-three children with ASD from four special schools were randomized into yoga (n = 23) and control (n = 20) group. A structured yoga program of 45 min for 12 weeks was delivered by trained yoga teachers who also tracked their daily responses. The Bruininks-Oseretsky Test of Motor Proficiency. Second Edition was used to assess both the groups pre- and postintervention. In conclusion, the study highlighted that yoga appears to have a positive impact on the gross motor rather than fine motor proficiency of children with ASD and is feasible to be delivered as group intervention in special schools.


Effect of ω-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial.
A promising treatment to prevent onset and improve outcomes in patients at ultrahigh risk for psychosis is dietary supplementation with long-chain ω-3 polyunsaturated fatty acids (PUFAs). To determine whether treatment with ω-3 PUFAs in combination with a high-quality psychosocial intervention (cognitive behavioral case management [CBCM]) is more effective than placebo plus CBCM. NEURAPRO, a double-blind, placebo-controlled, randomized clinical trial, was conducted from March 1, 2010, to September 30, 2014, in 10 specialized early psychosis treatment services in Australia, Asia, and Europe. The primary analysis used the intention-to-treat approach. A daily dose of 1.4 g of ω-3 PUFAs or placebo (paraffin oil), plus 20 or fewer sessions of CBCM over the 6-month study period. The primary outcome was transition to psychosis status at 6 months. The secondary outcomes were general levels of psychopathology and functioning, as assessed by the Brief Psychiatric Rating Scale (BPRS) (range, 24-168), Scale for the Assessment of Negative Symptoms (SANS) (range, 0-125), Montgomery-Åsberg Depression Rating Scale (MADRS) (range, 0-60), Young Mania Rating Scale (YMRS) (range, 0-44), Social and Occupational Functioning Assessment Scale (SOFAS) (range, 0-100), and the Global Functioning: Social and Role scale (range, 0-10). For SOFAS and Global Functioning: Social and Role scale, higher scores were better; for other measures, lower scores were better. In this study of 304 adults at ultrahigh risk for psychotic disorders, 153 (50.3%) received ω-3 PUFAs and 151 (49.7%) received placebo. In all, 139 (45.7%) were male; mean (SD) age was 19.1 (4.6) years. The Kaplan-Meier-estimated 6-month transition rates were 5.1% (95% CI, 1.3%-8.7%) in the control group and 6.7% (95% CI, 2.3%-10.8%) in the ω-3 PUFA group. At 12 months, the rates were 11.2% (95% CI, 5.5%-16.7%) in the control group and 11.5% (95% CI, 5.8%-16.9%) in the ω-3 PUFA group. No significant difference was observed between the transition rates of both groups (hazard ratio, 1.1; 95% CI, 0.55-2.23; P = .76, stratified log-rank test). This trial clearly failed to replicate the findings of the original single-center trial. The most likely explanation is that ω-3 PUFAs lack efficacy under these conditions. However, the lower-than-expected transition rate may have prevented a test of the main hypothesis. Given the substantial symptomatic and functional improvement in both groups, the other treatments received (ie, CBCM and antidepressants) likely produced a ceiling effect beyond which ω-3 PUFAs, even if effective, could not be shown to confer additional benefits. Nevertheless, the main conclusion is that ω-3 PUFAs are not effective under conditions where good quality, evidence-based psychosocial treatment is available. anzctr.org.au Identifier: 12608000475347.


Relationships of physical activity and sedentary behaviour with the previous and subsequent nights' sleep in children and youth: A systematic review and meta-analysis.
The interrelationships between sleep and daytime movement behaviours have been examined at interindividual level. Studies of within-person, temporal relationships of daytime physical activity (PA) and sedentary behaviour with the previous and subsequent nights' sleep are increasing. The present systematic review and meta-analysis synthesised the results of studies in school-aged children and youth. Eight databases (MEDLINE, PsycINFO, EMBASE, Global Health, PubMed, Web of Science, SPORTDiscus, and CINAHL) were searched for peer-reviewed articles that examined the association between daytime movement behaviours (including PA, sedentary time, or sedentary recreational screen time) and night-time sleep on the same day, or the association between night-time sleep and daytime movement behaviours the next day, in children and youth. A total of 11 studies comprising 9,622 children and youth aged 5-15 years met the inclusion criteria. Sedentary time was negatively associated with the subsequent night's sleep duration (r = -0.12, 95% confidence interval -0.23 to -0.00; I2 = 93%; p = .04). Positive relationships between PA and the previous or subsequent night's sleep duration were observed only for studies that adjusted for accelerometer wear time. There was some evidence suggesting that a longer sleep duration was associated with less sedentary time and a higher proportion of the daytime spent being physically active and vice versa, although the association was weak and based on a limited number of studies. From a clinical perspective, promotion of either sleep hygiene or daytime PA should be planned with considerations of the virtuous or vicious circle between these behaviours and monitor concurrent effects on the others.


Taare Zameen Par and dyslexic savants.
The film Taare Zameen Par (Stars upon the Ground) portrays the tormented life at school and at home of a child with dyslexia and his eventual success after his artistic talents are discovered by his art teacher at the boarding school. The film hints at a curious neurocognitive phenomenon of creativity in the midst of language disability, as exemplified in the lives of people like Leonardo da Vinci and Albert Einstein, both of whom demonstrated extraordinary creativity even though they were probably affected with developmental learning disorders. It has been hypothesized that a developmental delay in the dominant hemisphere most likely 'disinhibits' the nondominant parietal lobe, unmasking talents-artistic or otherwise-in some such individuals. It has been suggested that, in remedial training, children with learning disorders be encouraged to develop such hidden talents to full capacity, rather than be subjected to the usual overemphasis on the correction of the disturbed coded symbol operations.


Purified culture systems for bovine oviductal stromal cells.
Isolated stromal cells from the ampullary and isthmic parts of bovine oviductal tissues were cultured in monolayer and spheroid (cell aggregate) systems. Prostaglandin F2α (PGF) plays a crucial role in oviductal contraction and is produced by oviductal epithelial cells in cattle. Since stromal cells of many organs produce PGF, PGF production by bovine oviductal stromal cells was investigated. After PGF synthesis was confirmed, the utility of isolation and culture methods for oviductal stromal cells was evaluated by PGF production in the present study. The homogeneity of the cells was > 99%. PGF production of the cells was increased by tumor necrosis factor-α. The stromal cells aggregated and formed a spheroid by the treatments with several reagents. PGF production was higher in the spheroid culture than in the monolayer culture. The isolation and culture methods described here will facilitate studies of the physiological function of bovine oviductal stromal cells.


Simultaneous total intracranial volume and posterior fossa volume estimation using multi-atlas label fusion.
Total intracranial volume (TICV) is an essential covariate in brain volumetric analyses. The prevalent brain imaging software packages provide automatic TICV estimates. FreeSurfer and FSL estimate TICV using a scaling factor while SPM12 accumulates probabilities of brain tissues. None of the three provide explicit skull/CSF boundary (SCB) since it is challenging to distinguish these dark structures in a T1-weighted image. However, explicit SCB not only leads to a natural way of obtaining TICV (i.e., counting voxels inside the skull) but also allows sub-definition of TICV, for example, the posterior fossa volume (PFV). In this article, they proposed to use multi-atlas label fusion to obtain TICV and PFV simultaneously. The main contributions are: (1) TICV and PFV are simultaneously obtained with explicit SCB from a single T1-weighted image. (2) TICV and PFV labels are added to the widely used BrainCOLOR atlases. (3) Detailed mathematical derivation of non-local spatial STAPLE (NLSS) label fusion is presented. As the skull is clearly distinguished in CT images, we use a semi-manual procedure to obtain atlases with TICV and PFV labels using 20 subjects who both have a MR and CT scan. The proposed method provides simultaneous TICV and PFV estimation while achieving more accurate TICV estimation compared with FreeSurfer, FSL, SPM12, and the previously proposed STAPLE based approach. The newly developed TICV and PFV labels for the OASIS BrainCOLOR atlases provide acceptable performance, which enables simultaneous TICV and PFV estimation during whole brain segmentation. The NLSS method and the new atlases have been made freely available. Hum Brain Mapp 38:599-616, 2017. © 2016 Wiley Periodicals, Inc.


Epidemic of mesothelioma in Egypt.
Asbestos has been recognized in Egypt since a long time as ancient Egyptians were using it in mummification. Mesothelioma in Egypt is mainly attributed to environmental origin with a high incidence of women and young adults affected. The incidence of mesothelioma is rising in Egypt. Epidemiological data for 635 malignant mesothelioma (MM) patients over 4 years in the third Millennium were collected from the National Cancer Institute (NCI), Cairo University and Abbassia Chest hospital. This number is more than four times the number diagnosed in the previous 11 years at NCI. A clinicopathological study was done for 100 malignant pleural mesothelioma (MPM) patients and showed that asbestos exposure and SV40 positivity were evident in 67% and 60% of cases, respectively. The median survival was 14.3 months and the 1 and 2 year survival rates were 60% and 27%, respectively. Evaluation of p53 and pRb immunohistochemically showed that pRb alteration was related to poor survival. Other biological prognostic factors such as EGFR, HER-2, glutathione S transferase (GST) and MDR were evaluated in 50 cases. Overexpression of EGFR was correlated with lack of clinical benefit and poor survival. GST potentiated the effect of EGFR on survival. The use of EGFR inhibitors may have a role in the treatment of MM. Asbestos in Cairo is a silent killer and measures toward eliminating it entirely or at least strictly controlling human contact with this dangerous carcinogen have to be taken in order to combat the coming epidemic of mesothelioma in Egypt.


[Q fever: an overview].
Q fever, a zoonosis caused by the gram-negative bacterium Coxiella burnetii, occurs worldwide and affects both humans and animals. Ruminants are considered to be the main source of infection of humans, with the main route of infection being through inhalation of the organism of fine-particle aerosols. Abortion is the main clinical sign in ruminants. During and after abortion, large quantities of the bacterium are shed via the placenta and other vaginal secretions. The bacterium may also be present in faeces and milk. The bacterium can survive for a long time in the environment after shedding and can be spread over long distances. Seroprevalence among cattle is rather high in the Netherlands and in many other countries. Infection is diagnosed by detecting antibodies against the bacterium or the bacterium itself by means of a PCR method. The efficacy of using antibiotics or vaccines for treatment or prevention of the disease in cattle is still unclear and there are currently no effective disease control programmes.


Which type 2 diabetes mellitus patients should be screened for subclinical Cushing's syndrome?
Diabetes or impaired glucose tolerance are common in patients with Cushing's syndrome (CS). In this study we investigated the incidence of subclinical Cushing's syndrome (SCS) in type 2 diabetic patients with poor and good metabolic control and the relationship between blood glucose and cortisol levels. A total of 400 type 2 diabetes mellitus (T2DM) patients (Group A, HbA1c ≥8%, n=250; Group B, HbA1c ≤6.5%, n=150) were included in the study. Biochemical tests followed by the 1 mg dexamethasone suppression test (DST) were performed. If post-DST cortisol levels were above 1.8 μg/dl (non-suppressed group), the 2 mg DST test was performed for 2 days. Among the patients, post-DST cortisol of at least 1.8 μg/dL and midnight serum cortisol levels of at least 7.5 μg/dL confirmed the diagnosis of CS. While SCS was observed in 5 patients (2%) in Group A, no case was observed in group B. There was a statistically significant difference between groups for basal cortisol and post-DST cortisol results (p<0.001 and p<0.001, respectively). Microvascular complication rates were higher in the non-suppressed group (p=0.007). Post-DST cortisol levels had a positive correlation with the number of complications and HbA1c levels (respectively r=0.213, p<0.001, and r=0.191, p<0.001). Multivariate regression analysis revealed that durations of DM, HbA1c level, and post 1 mg DST cortisol levels were associated with the number of complications. This study shows the presence of SCS in a notable number in T2DM patients having poor metabolic control. Screening with 1 mg and 2 mg DST of T2DM patients with poor metabolic control who are also obese and hypertensive and have microvascular complications may be an appropriate method for detection of SCS.


Regression of intracardiac thrombus after embolic stroke.
Using two-dimensional echocardiography, we studied the pathophysiology of intracardiac thrombus regression accompanied by anticoagulant therapy in 82 consecutive patients with acute cardiogenic cerebral embolism. We noted intracardiac thrombus in 15 patients; nine of the 15 were started on anticoagulant therapy with warfarin potassium to maintain the prothrombin time between 2.5 and 3.5 (international normalized ratio). Serial two-dimensional echocardiograms were obtained for these nine patients before and after anticoagulation, with the plasma levels of fibrinopeptide A, fibrinopeptide B beta 15-42, and D-dimer measured at the same time. In eight of the nine patients the intracardiac thrombi gradually decreased in size while the plasma level of fibrinopeptide A fell to within the normal range and the plasma levels of fibrinopeptide B beta 15-42 and D-dimer remained above the normal ranges. In the other patient the thrombus disappeared, with embolization to the right arm immediately after starting anticoagulant therapy. Mobile or small thrombi regressed earlier than nonmobile or large ones. We conclude that regression of intracardiac thrombi after anticoagulation may be based on the relative predominance of plasma fibrinolytic activity over anticoagulation-inhibited thrombin activity.


Agonist-induced internalization of metabotropic glutamate receptor 1A: structural determinants for protein kinase C- and G protein-coupled receptor kinase-mediated internalization.
To investigate the role of the intracellular C-terminal tail of the rat metabotropic glutamate receptor 1a (mGlu1a) in receptor regulation, we constructed three C-terminal tail deletion mutants (Arg847stop, DM-I; Arg868stop, DM-II; Val893stop, DM-III). Quantification of glutamate-induced internalization provided by ELISA indicated that DM-III, like the wild-type mGlu1a, underwent rapid internalization whilst internalization of DM-I and DM-II was impaired. The selective inhibitor of protein kinase C (PKC), GF109203X, which significantly reduced glutamate-induced mGlu1a internalization, had no effect on the internalization of DM-I, DM-II, or DM-III. In addition activation by carbachol of endogenously expressed M1 muscarinic acetylcholine receptors, which induces PKC- and Ca2+-calmodulin-dependent protein kinase II-dependent internalization of mGlu1a, produced negligible internalization of the deletion mutants. Co-expression of a dominant negative mutant form of G protein-coupled receptor kinase 2 (DNM-GRK2; Lys220Arg) significantly attenuated glutamate-induced internalization of mGlu1a and DM-III, whilst internalization of DM-I and DM-II was not significantly affected. The glutamate-induced internalization of mGlu1a and DM-III, but not of DM-I or DM-II, was inhibited by expression of DNM-arrestin [arrestin-2(319-418)]. In addition glutamate-induced rapid translocation of arrestin-2-Green Fluorescent Protein (arr-2-GFP) from cytosol to membrane was only observed in cells expressing mGlu1a or DM-III. Functionally, in cells expressing mGlu1a, glutamate-stimulated inositol phosphate accumulation was increased in the presence of PKC inhibition, but so too was that in cells expressing DM-II and DM-III. Together these results indicate that different PKC mechanisms regulate the desensitization and internalization of mGlu1a. Furthermore, PKC regulation of mGlu1a internalization requires the distal C terminus of the receptor (Ser894-Leu1199), whilst in contrast glutamate-stimulated GRK- and arrestin-dependent regulation of this receptor depends on a region of 25 amino acids (Ser869-Val893) in the proximal C-terminal tail.


Genomic composition and dynamics among Methanomicrobiales predict adaptation to contrasting environments.
Members of the order Methanomicrobiales are abundant, and sometimes dominant, hydrogenotrophic (H2-CO2 utilizing) methanoarchaea in a broad range of anoxic habitats. Despite their key roles in greenhouse gas emissions and waste conversion to methane, little is known about the physiological and genomic bases for their widespread distribution and abundance. In this study, we compared the genomes of nine diverse Methanomicrobiales strains, examined their pangenomes, reconstructed gene flow and identified genes putatively mediating their success across different habitats. Most strains slowly increased gene content whereas one, Methanocorpusculum labreanum, evidenced genome downsizing. Peat-dwelling Methanomicrobiales showed adaptations centered on improved transport of scarce inorganic nutrients and likely use H+ rather than Na+ transmembrane chemiosmotic gradients during energy conservation. In contrast, other Methanomicrobiales show the potential to concurrently use Na+ and H+ chemiosmotic gradients. Analyses also revealed that the Methanomicrobiales lack a canonical electron bifurcation system (MvhABGD) known to produce low potential electrons in other orders of hydrogenotrophic methanogens. Additional putative differences in anabolic metabolism suggest that the dynamics of interspecies electron transfer from Methanomicrobiales syntrophic partners can also differ considerably. Altogether, these findings suggest profound differences in electron trafficking in the Methanomicrobiales compared with other hydrogenotrophs, and warrant further functional evaluations.


Cocaine differentially inhibits neuronal differentiation and proliferation in vitro.
The outcome of in utero cocaine exposure is unclear. To determine if cocaine affects neuronal growth and differentiation, we used PC-12 cells, which have a mitogenic response to IGF-I and differentiate into neurons on exposure to nerve growth factor. Differentiation was quantified as neurite extension after a 72-h exposure to 20 ng/ml nerve growth factor (dosage at 50% maximal effectiveness) and cocaine doses ranging from 0.01 to 10 micrograms/ml. The results were 49 +/- 2, 40 +/- 3, 29 +/- 2, 23 +/- 2, and 12 +/- 2% differentiation with respective cocaine concentrations of 0, 0.01, 0.1, 1, and 10 micrograms/ml (P < 0.0001). Cocaine stability studies showed insignificant spontaneous hydrolysis under the conditions of this study. Cocaine did not affect cell viability or number, but had a relatively modest, statistically significant (P < 0.001) inhibitory effect on IGF-I-stimulated thymidine incorporation. The dose-response curves for differentiation vs mitogenic response differed significantly (P = 0.021). Therefore, cocaine inhibition of these processes is probably mediated by different mechanisms, and not caused by generalized toxicity. To our knowledge, this is the first demonstration of cocaine effects on neuronal multiplication and differentiation in vitro. The results suggest in utero exposure may directly impair brain development.


Memory effects of speech and gesture binding: cortical and hippocampal activation in relation to subsequent memory performance.
In human face-to-face communication, the content of speech is often illustrated by coverbal gestures. Behavioral evidence suggests that gestures provide advantages in the comprehension and memory of speech. Yet, how the human brain integrates abstract auditory and visual information into a common representation is not known. Our study investigates the neural basis of memory for bimodal speech and gesture representations. In this fMRI study, 12 participants were presented with video clips showing an actor performing meaningful metaphoric gestures (MG), unrelated, free gestures (FG), and no arm and hand movements (NG) accompanying sentences with an abstract content. After the fMRI session, the participants performed a recognition task. Behaviorally, the participants showed the highest hit rate for sentences accompanied by meaningful metaphoric gestures. Despite comparable old/new discrimination performances (d') for the three conditions, we obtained distinct memory-related left-hemispheric activations in the inferior frontal gyrus (IFG), the premotor cortex (BA 6), and the middle temporal gyrus (MTG), as well as significant correlations between hippocampal activation and memory performance in the metaphoric gesture condition. In contrast, unrelated speech and gesture information (FG) was processed in areas of the left occipito-temporal and cerebellar region and the right IFG just like the no-gesture condition (NG). We propose that the specific left-lateralized activation pattern for the metaphoric speech-gesture sentences reflects semantic integration of speech and gestures. These results provide novel evidence about the neural integration of abstract speech and gestures as it contributes to subsequent memory performance.


Clostridium difficile in paediatric populations.
An increase in Clostridium difficile infection incidence has been observed among hospitalized children in the United States. The present statement, targeted at clinicians caring for infants and children in community and institutional settings, summarizes the relevant information relating to the role of C difficile in childhood diarrhea and provides recommendations for diagnosis, prevention and treatment. Significant differences between adult and paediatric risk factors and disease are discussed, along with emerging therapies. The relationship between age and disease severity in children with a newly emergent and more fluoroqinolone-resistant strain of C difficile (North American Pulse-field type-1 [NAP1]) remains unknown. The importance of antimicrobial stewardship as a preventive strategy is highlighted. This statement replaces a previous Canadian Paediatric Society position statement on C difficile published in 2000.


Fast wavelet based functional models for transcriptome analysis with tiling arrays.
For a better understanding of the biology of an organism, a complete description is needed of all regions of the genome that are actively transcribed. Tiling arrays are used for this purpose. They allow for the discovery of novel transcripts and the assessment of differential expression between two or more experimental conditions such as genotype, treatment, tissue, etc. In tiling array literature, many efforts are devoted to transcript discovery, whereas more recent developments also focus on differential expression. To our knowledge, however, no methods for tiling arrays have been described that can simultaneously assess transcript discovery and identify differentially expressed transcripts. In this paper, we adopt wavelet based functional models to the context of tiling arrays. The high dimensionality of the data triggered us to avoid inference based on Bayesian MCMC methods. Instead, we introduce a fast empirical Bayes method that provides adaptive regularization of the functional effects. A simulation study and a case study illustrate that our approach is well suited for the simultaneous assessment of transcript discovery and differential expression in tiling array studies, and that it outperforms methods that accomplish only one of these tasks.


Face photo-sketch synthesis and recognition.
In this paper, we propose a novel face photo-sketch synthesis and recognition method using a multiscale Markov Random Fields (MRF) model. Our system has three components: 1) given a face photo, synthesizing a sketch drawing; 2) given a face sketch drawing, synthesizing a photo; and 3) searching for face photos in the database based on a query sketch drawn by an artist. It has useful applications for both digital entertainment and law enforcement. We assume that faces to be studied are in a frontal pose, with normal lighting and neutral expression, and have no occlusions. To synthesize sketch/photo images, the face region is divided into overlapping patches for learning. The size of the patches decides the scale of local face structures to be learned. From a training set which contains photo-sketch pairs, the joint photo-sketch model is learned at multiple scales using a multiscale MRF model. By transforming a face photo to a sketch (or transforming a sketch to a photo), the difference between photos and sketches is significantly reduced, thus allowing effective matching between the two in face sketch recognition. After the photo-sketch transformation, in principle, most of the proposed face photo recognition approaches can be applied to face sketch recognition in a straightforward way. Extensive experiments are conducted on a face sketch database including 606 faces, which can be downloaded from our Web site (http://mmlab.ie.cuhk.edu.hk/facesketch.html).


Is cognitive-behavioral therapy more effective than other therapies? A meta-analytic review.
Cognitive-behavioral therapy (CBT) is effective for a range of psychiatric disorders. However, it remains unclear whether CBT is superior to other forms of psychotherapy, and previous quantitative reviews on this topic are difficult to interpret. The aim of the present quantitative review was to determine whether CBT yields superior outcomes to alternative forms of psychotherapy, and to examine the relationship between differential outcome and study-specific variables. From a computerized literature search through September 2007 and references from previous reviews, English-language articles were selected that described randomized controlled trials of CBT vs. another form of psychotherapy. Of these, only those in which the CBT and alternative therapy condition were judged to be bona fide treatments, rather than "intent-to-fail" conditions, were retained for analysis (28 articles representing 26 studies, N=1981). Four raters identified post-treatment and follow-up effect size estimates, as well as study-specific variables including (but not limited to) type of CBT and other psychotherapy, sample diagnosis, type of outcome measure used, and age group. Studies were rated for methodological adequacy including (but not limited to) the use of reliable and valid measures and independent evaluators. Researcher allegiance was determined by contacting the principal investigators of the source articles. CBT was superior to psychodynamic therapy, although not interpersonal or supportive therapies, at post-treatment and at follow-up. Methodological strength of studies was not associated with larger or smaller differences between CBT and other therapies. Researchers' self-reported allegiance was positively correlated with the strength of CBT's superiority; however, when controlling for allegiance ratings, CBT was still associated with a significant advantage. The superiority of CBT over alternative therapies was evident only among patients with anxiety or depressive disorders. These results argue against previous claims of treatment equivalence and suggest that CBT should be considered a first-line psychosocial treatment of choice, at least for patients with anxiety and depressive disorders.


Satisfaction in child and adolescent mental health services: translating users' feedback into measurement.
The present research addressed gaps in our current understanding of validity and quality of measurement provided by patient reported experience measures. We established the psychometric properties of a freely available experience of service questionnaire (ESQ), based on responses from 7,067 families of patients across 41 UK providers of child and adolescent mental health services, using the two-level latent trait modeling. Responses to the ESQ were subject to strong 'halo' effects, which were thought to represent the overall positive or negative affect towards one's treatment. Two strongly related constructs measured by the ESQ were interpreted as specific aspects of global satisfaction, namely satisfaction with care, and with environment. The Care construct was sensitive to differences between less satisfied patients, facilitating individual and service-level problem evaluation. The effects of nesting within service providers were strong, with parental reports being the most reliable source of data for the between-provider comparisons. We provide a scoring protocol for converting the hand-scored ESQ to the model-based population-referenced scores with supplied standard errors, which can be used for benchmarking services as well as individual evaluations.


More Comprehensive Care Among Family Physicians is Associated with Lower Costs and Fewer Hospitalizations.
Comprehensiveness is lauded as 1 of the 5 core virtues of primary care, but its relationship with outcomes is unclear. We measured associations between variations in comprehensiveness of practice among family physicians and healthcare utilization and costs for their Medicare beneficiaries. We merged data from 2011 Medicare Part A and B claims files for a complex random sample of family physicians engaged in direct patient care, including 100% of their claimed care of Medicare beneficiaries, with data reported by the same physicians during their participation in Maintenance of Certification for Family Physicians (MC-FP) between the years 2007 and 2011. We created a measure of comprehensiveness from mandatory self-reported survey items as part of MC-FP examination registration. We compared this measure to another derived from Medicare's Berenson-Eggers Type of Service (BETOS) codes. We then examined the association between the 2 measures of comprehensiveness and hospitalizations, Part B payments, and combined Part A and B payments. Our full family physician sample consists of 3,652 physicians providing the plurality of care to 555,165 Medicare beneficiaries. Of these, 1,133 recertified between 2007 and 2011 and cared for 185,044 beneficiaries. There was a modest correlation (0.30) between the BETOS and self-reported comprehensiveness measures. After adjusting for beneficiary and physician characteristics, increasing comprehensiveness was associated with lower total Medicare Part A and B costs and Part B costs alone, but not with hospitalizations; the association with spending was stronger for the BETOS measure than for the self-reported measure; higher BETOS scores significantly reduced the likelihood of a hospitalization. Increasing family physician comprehensiveness of care, especially as measured by claims measures, is associated with decreasing Medicare costs and hospitalizations. Payment and practice policies that enhance primary care comprehensiveness may help "bend the cost curve."


The views of sick-listed employees' immediate superiors on co-operation in vocational rehabilitation.
The purpose of this research was to investigate the views of sick-listed employees' immediate superiors on co-operation in vocational rehabilitation before and during a systematic, multi-professional, client-centred, solution-oriented co-operation project in vocational rehabilitation (SMVR intervention). A same-subject study with a questionnaire was used, with 95 immediate superiors giving their views on co-operation both before and during the SMVR intervention. The immediate superiors felt that the SMVR intervention was successful in promoting co-operation, and reported a significant decrease in referrals of employees from one organisation to another without the problem being resolved. Hence SMVR co-operation was experienced positively by the immediate superiors and in fact led to a joint responsibility in finding solutions. The immediate superiors saw greater possibilities than before for employees to resume regular or other jobs during the SMVR intervention. A more elaborate co-operation model such as the SMVR intervention increased the immediate superiors' experience of successful vocational rehabilitation. Organizations seeking to increase efficiency in vocational rehabilitation might well analyse their work methods and improve their forms of co-operation.


Intestinal absorption of dietary cholesteryl ester is decreased but retinyl ester absorption is normal in carboxyl ester lipase knockout mice.
Carboxyl ester lipase (CEL; EC 22.214.171.124) hydrolyzes cholesteryl esters and retinyl esters in vitro. In vivo, pancreatic CEL is thought to liberate cholesterol and retinol from their esters prior to absorption in the intestine. CEL is also a major lipase in the breast milk of many mammals, including humans and mice, and is thought to participate in the processing of triglycerides to provide energy for growth and development while the pancreas of the neonate matures. Other suggested roles for CEL include the direct facilitation of the intestinal absorption of free cholesterol and the modification of plasma lipoproteins. Mice with different CEL genotypes [wild type (WT), knockout (CELKO), heterozygote] were generated to study the functions of CEL in a physiological system. Mice grew and developed normally, independent of the CEL genotype of the pup or nursing mother. Consistent with this was the normal absorption of triglyceride in CELKO mice. The absorption of free cholesterol was also not significantly different between CELKO (87 +/- 26%, mean +/- SD) and WT littermates (76 +/- 10%). Compared to WT mice, however, CELKO mice absorbed only about 50% of the cholesterol provided as cholesteryl ester (CE). There was no evidence for the direct intestinal uptake of CE or for intestinal bacterial enzymes that hydrolyze it, suggesting that another enzyme besides CEL can hydrolyze dietary CE in mice. Surprisingly, CELKO and WT mice absorbed similar amounts of retinol provided as retinyl ester (RE). RE hydrolysis, however, was required for absorption, implying that CEL was not the responsible enzyme. The changes in plasma lipid and lipoprotein levels to diets with increasing lipid content were similar in mice of all three CEL genotypes. Overall, the data indicate that in the mouse, other enzymes besides CEL participate in the hydrolysis of dietary cholesteryl esters, retinyl esters, and triglycerides.


Cell transformation and genotoxicity induced by bis(2, 3-dichloro-1-propyl) ether.
Bis(dichloropropyl) ether isomers have been identified in a petrochemical plant effluent through a toxicity identification evaluation study in the United States. They have also been observed in the microgram per liter range along one of the largest rivers in Europe, the Elbe River. In the present investigation, the genotoxic and transforming activity of a bis(dichloropropyl) ether isomer, bis(2,3-dichloro-1-propyl) ether, was assayed in vitro. The results demonstrate that bis(2,3-dichloro-1-propyl) ether is a potent mutagen in Salmonella typhimurium strains TA 100, TA 1535, and to a lesser extent in strain TA 98, but only when tested in the presence of a metabolic activation system (S9 mix). We have also investigated the induction of micronuclei by bis(2,3-dichloro-1-propyl) ether in the metabolically competent cell line, MCL-5. A linear, dose-dependent increase in micronuclei was observed following exposure to bis(2,3-dichloro-1-propyl) ether. The DNA strand-breaking capacity of this chemical was assessed in the alkaline single-cell gel electrophoresis ("comet") assay with MCL-5 cells. Bis(2,3-dichloro-1-propyl) ether clearly induced DNA strand breaks in the 4.5-45.5 microg/ml dose range. The ether also induced malignant transformation in C3H/M2 mouse fibroblasts after metabolic activation (S9 mix). Thus, it must be suspected that bis(2, 3-dichloro-1-propyl) ether may possess a carcinogenic potential. Since the compound along with its isomers is present in considerable concentrations in surface water, their elimination is a matter of significant public concern.


Effect of Thermocycling on Biaxial Flexural Strength of CAD/CAM, Bulk Fill, and Conventional Resin Composite Materials.
New resin-based restorative materials have been developed, such as computer-aided design/computer-aided manufacturing (CAD/CAM) and bulk-fill composites, as an alternative to traditional layering techniques. This study evaluated the biaxial flexural strength (BFS) before and after thermocycling of five different resin composites: one hybrid resin/ceramic CAD/CAM indirect material, Lava Ultimate CAD-CAM Restorative (LU, 3M Oral Care); a conventional composite, Filtek Z350 XT (Z350, 3M Oral Care); two bulk-fill composites, Tetric N-Ceram Bulk Fill (TBF, Ivoclar Vivadent) and Filtek Bulk Fill (FBF, 3M Oral Care); and one bulk-fill flow resin composite, Filtek Bulk Fill Flow (FBFF, 3M Oral Care). Three hundred disc-shaped specimens (6.5 mm in diameter and 0.5 mm thick) were fabricated and divided into five groups (n=30 for each composite and condition). The BFS test was performed in a universal testing machine at a crosshead speed of 0.5 mm/min immediately (i, 24 hours) and after thermocycling (a, 500 thermal cycles of 5°C to 55°C with a 30-second dwell time). The Weibull modulus (m) and characteristic stress (η) were calculated, and a contour plot was used (m vs η) to detect differences between groups (95% two-sided confidence intervals). Significantly higher characteristic stress was observed for LUi (286.6 MPa) and Z350i (248.8 MPa) compared to the bulk-fill groups (FBFi=187.9 MPa, FBFFi=175.9 MPa, TBFi=149.9 MPa), with no differences between LUi and Z350i. Thermocycling significantly decreased the characteristic stress of all groups with the highest values observed for LUa (186.7 MPa) and Z350a (188.9 MPa) and the lowest for FBFFa (90.3 MPa). Intermediate values were observed for FBFa (151.6 MPa) and TBFa (122.8 MPa). The Weibull modulus decreased only for FBFa compared to FBFi. Composition and thermocycling significantly influenced the biaxial flexural strength of resin composite materials.


The tomato UV-damaged DNA-binding protein-1 (DDB1) is implicated in pathogenesis-related (PR) gene expression and resistance to Agrobacterium tumefaciens.
Plants defend themselves against potential pathogens via the recognition of pathogen-associated molecular patterns (PAMPs). However, the molecular mechanisms underlying this PAMP-triggered immunity (PTI) are largely unknown. In this study, we show that tomato HP1/DDB1, coding for a key component of the CUL4-based ubiquitin E3 ligase complex, is required for resistance to Agrobacterium tumefaciens. We found that the DDB1-deficient mutant (high pigment-1, hp1) is susceptible to nontumorigenic A. tumefaciens. The efficiency of callus generation from the hp1 cotyledons was extremely low as a result of the necrosis caused by Agrobacterium infection. On infiltration of nontumorigenic A. tumefaciens into leaves, the hp1 mutant moderately supported Agrobacterium growth and developed disease symptoms, but the expression of the pathogenesis-related gene SlPR1a1 and several PTI marker genes was compromised at different levels. Moreover, exogenous application of salicylic acid (SA) triggered SlPR1a1 gene expression and enhanced resistance to A. tumefaciens in wild-type tomato plants, whereas these SA-regulated defence responses were abolished in hp1 mutant plants. Thus, HP1/DDB1 may function through interaction with the SA-regulated PTI pathway in resistance against Agrobacterium infection.


Variation in virulence of West Nile virus strains for house sparrows (Passer domesticus).
The observation of avian mortality associated with West Nile virus (WNV) infection has become a hallmark epidemiologic feature in the recent emergence of this pathogen in Israel and North America. To determine if phenotypic differences exist among different WNV isolates, we exposed house sparrows (Passer domesticus) to low passage, lineage 1 WNV strains from North America (NY99), Kenya (KEN), and Australia (KUN; also known as Kunjin virus). House sparrows inoculated with the NY99 and KEN strains experienced similar mortality rates and viremia profiles. The KUN strain elicited significantly lower-titered viremia when compared with the other strains and induced no mortality. This study suggests that natural mortality in house sparrows due to Old World strains of WNV may be occurring where the KEN strain occurs.


The health co-benefits of climate change policies: doctors have a responsibility to future generations.
Mitigating climate change presents unrivalled opportunities for improving public health. The policies that need to be implemented to reduce greenhouse gas emissions will also bring about substantial reductions in heart disease, cancer, obesity, diabetes, road deaths and injuries, and air pollution. The health benefits arise because climate change policies necessarily impact on two of the most important determinants of health: human nutrition and human movement. Although the health co-benefits of climate change policies are increasingly recognised by health professionals they are not widely appreciated by those responsible for policy. Because the existence of important health co-benefits will dramatically reduce the cost to society of taking strong action to mitigate climate change, failure to appreciate their importance could have serious environmental consequences. Health professionals have an urgent responsibility to ensure that the health benefits of environmental policies are understood by the public and by policymakers.


Heart and Lungs Protection Technique for Cardiac Surgery with Cardiopulmonary Bypass.
Cardioplegic cardiac arrest with subsequent ischemic-reperfusion injuries can lead to the development of inflammation of the myocardium, leucocyte activation, and release of cardiac enzymes. Flow reduction to the bronchial arteries, causing low-flow lung ischemia, leads to the development of a pulmonary regional inflammatory response. Hypoventilation during cardiopulmonary bypass (CPB) is responsible for development of microatelectasis, hydrostatic pulmonary edema, poor compliance, and a higher incidence of infection. Based on these facts, prevention methods of these complications were developed. The aim of this study was to evaluate constant coronary perfusion (CCP) and the "beating heart" in combination with pulmonary artery perfusion (PAP) and "ventilated lungs" technique for heart and lung protection in cardiac surgery with CPB. After ethical approval and written informed consent, 80 patients undergoing cardiac surgery with normothermic CPB were randomized in three groups. In the first group (22 patients), the crystalloid cardioplegia without lung ventilation/perfusion techniques were used. In the second group (30 patients), the CCP and "beating heart" without lung ventilation/perfusion techniques were used. In the third group (28 patients), the CCP with PAP and lung ventilation techniques were used. Clinical, functional parameters, myocardial damage markers (CK MB level), oxygenation index, and lung compliance were investigated. There were higher rates of spontaneous cardiac recovery and lower doses of inotrops in the second and third groups. Myocardial contractility function was better preserved in the second and third groups. The post-operative levels of CK-MB were lower than in control group. Three hours after surgery CK-MB levels in the second and third groups were lower by 38.1% and 33.3%, respectively. Eight hours after surgery, CK-MB levels were lower in the second and third groups by 45.9% and 47.7%, respectively. 24 hours after surgery, CK-MB levels were lower in the second and third groups by 42.0% and 42.6%, respectively, and lower by 29.7% and 27.4% 48 hours after surgery, respectively. Normalization of CK-MB levels were registered earlier in second and third groups (within 24 hours) than the control group. Oxygenation index and lung compliance were significantly higher in the third group after CPB. Our technique improved myocardial and lung function in patients, but larger prospective randomized trials are needed to definitively assess the protective effects of this technique.


Controlled observations in critical care medicine: the therapeutic trial.
The practice of critical care medicine revolves around the monitoring of patients to identify acute physiologic deterioration and the titration of therapies aimed at supporting internal homeostasis. Central to this practice is the evaluation of therapies or stresses designed to assess homeostatic reserve and to uncover pathologic processes. Both the cardiovascular and respiratory systems have received particular attention because of the ease with which specific haemodynamic and respiratory parameters can be measured, the ability to modulate their status with therapies, and the intimacy of both cardiovascular and respiratory status to overall homeostasis. These forms of assessment are referred to as clinical trials, and if performed in a rigorous fashion are referred to as controlled clinical trials. Clinical trials form much of the basis for titration of therapy, wherein a specific therapy is adjusted so as to optimise its effectiveness in an individual. Titration is typically done once a diagnosis has already been made or a treatment identified, such as with the titration of antihypertensive therapy in either hospital or outpatient setting. This review will focus on the exploratory aspect of clinical trials wherein a specific manoeuvre is performed to determine either the aetiology or severity of a pathophysiologic problem.


An integrative literature review of small food store research across urban and rural communities in the U.S.
The purpose of this review was to identify how rural and urban food access differs across small food stores as well as the types of research strategies and methodologies that have been applied in each setting in the U.S. Manuscripts were included in the review if they were published in English over the past ten years, with a clear delineation between urban and/or rural, conducted in the U.S., and reported data from small food store research. After elimination, 19 manuscripts representing rural (n = 5) and urban (n = 14) settings were included in the final review. The review was conducted in Nebraska between January 2015 and May 2015. Findings from the reviewed manuscripts revealed that rural communities might face different challenges with healthy food access in small food stores when compared to urban settings. In particular, small food stores in rural areas lacked healthy food options largely because storeowners perceived that their customers would not purchase healthier items and due to challenges with distribution. Conversely, studies reporting on small food stores in urban areas suggest challenges with transportation and safety concerns. Research on small food stores is nascent and further research, especially intervention studies, is needed. Further, less evidence exists on healthy food access, in particular intervention testing on small food store research in rural areas.


Taxonomic revision of Phascogale tapoatafa (Meyer, 1793) (Dasyuridae; Marsupialia), including descriptions of two new subspecies and confirmation of P. pirata Thomas, 1904 as a 'Top End' endemic.
The Australian Brush-tailed Phascogale (Phascogale tapoatafa sensu lato) has a broad but highly fragmented distribution around the periphery of the Australian continent and all populations are under significant ongoing threat to survival. A new appraisal of morphological and molecular diversity within the group reveals that the population in the 'Top End' of the Northern Territory is specifically distinct from all others, including those in the Kimberley region of Western Australia to the west and on Cape York of Queensland to the east. The name P. pirata Thomas, 1904 is available for the 'Top End' taxon. Three geographically disjunct populations are distinguished at subspecies level within P. tapoatafa on a suite of external and cranio-dental features; these are found in southeast Australia from South Australia to mid-coastal Queensland (nominotypical tapoatafa), southwest Western Australia (wambenger subsp. nov.), and the Kimberley region of Western Australia (kimberleyensis subsp. nov.). A potential fourth subspecies occurs on Cape York but remains too poorly represented in collections for adequate characterization. Molecular divergence estimates based on partial sequences of the mitochondrial cytochrome b gene indicate that the range disjunction across southern Australia probably dates from the Late Pliocene, with the multiple disjunctions across northern Australia being more recent though almost certainly exceeding 400,000 years. An argument is made for the continued use of the subspecies rank in Australian mammalogy, despite a general lack of consistency in its current application.


A multiprotein supercomplex controlling oncogenic signalling in lymphoma.
B cell receptor (BCR) signalling has emerged as a therapeutic target in B cell lymphomas, but inhibiting this pathway in diffuse large B cell lymphoma (DLBCL) has benefited only a subset of patients1. Gene expression profiling identified two major subtypes of DLBCL, known as germinal centre B cell-like and activated B cell-like (ABC)2,3, that show poor outcomes after immunochemotherapy in ABC. Autoantigens drive BCR-dependent activation of NF-κB in ABC DLBCL through a kinase signalling cascade of SYK, BTK and PKCβ to promote the assembly of the CARD11-BCL10-MALT1 adaptor complex, which recruits and activates IκB kinase4-6. Genome sequencing revealed gain-of-function mutations that target the CD79A and CD79B BCR subunits and the Toll-like receptor signalling adaptor MYD885,7, with MYD88(L265P) being the most prevalent isoform. In a clinical trial, the BTK inhibitor ibrutinib produced responses in 37% of cases of ABC1. The most striking response rate (80%) was observed in tumours with both CD79B and MYD88(L265P) mutations, but how these mutations cooperate to promote dependence on BCR signalling remains unclear. Here we used genome-wide CRISPR-Cas9 screening and functional proteomics to determine the molecular basis of exceptional clinical responses to ibrutinib. We discovered a new mode of oncogenic BCR signalling in ibrutinib-responsive cell lines and biopsies, coordinated by a multiprotein supercomplex formed by MYD88, TLR9 and the BCR (hereafter termed the My-T-BCR supercomplex). The My-T-BCR supercomplex co-localizes with mTOR on endolysosomes, where it drives pro-survival NF-κB and mTOR signalling. Inhibitors of BCR and mTOR signalling cooperatively decreased the formation and function of the My-T-BCR supercomplex, providing mechanistic insight into their synergistic toxicity for My-T-BCR+ DLBCL cells. My-T-BCR supercomplexes characterized ibrutinib-responsive malignancies and distinguished ibrutinib responders from non-responders. Our data provide a framework for the rational design of oncogenic signalling inhibitors in molecularly defined subsets of DLBCL.


Role of interface correlation in light scattering by a multilayer.
Four industries prepared optical coatings with a common design that permits an easy determination of cross-correlation laws between the rough interfaces in the stack. Different pairs of materials and deposition processes were used. After clarifying the differences between scalar and vector theories of light scattering caused by rough interfaces in optical multilayers, we compare the experimental values with both theories. Factors such as variations of correlation with spatial frequency, residual roughness, and slight errors in the design are taken into account for comparison with the vector theory of angular scattering. Correlation of the interface roughnesses is found to be high for practically all coatings. However, at low scatter-loss levels, scattering by localized defects in the coatings appears to dominate over the scattering caused by rough interfaces.


ADAMTS7B, the full-length product of the ADAMTS7 gene, is a chondroitin sulfate proteoglycan containing a mucin domain.
We have characterized ADAMTS7B, the authentic full-length protein product of the ADAMTS7 gene. ADAMTS7B has a domain organization similar to that of ADAMTS12, with a total of eight thrombospondin type 1 repeats in its ancillary domain. Of these, seven are arranged in two distinct clusters that are separated by a mucin domain. Unique to the ADAMTS family, ADAMTS7B is modified by attachment of the glycosaminoglycan chondroitin sulfate within the mucin domain, thus rendering it a proteoglycan. Glycosaminoglycan addition has potentially important implications for ADAMTS7B cellular localization and for substrate recognition. Although not an integral membrane protein, ADAMTS7B is retained near the cell surface of HEK293F cells via interactions involving both the ancillary domain and the prodomain. ADAMTS7B undergoes removal of the prodomain by a multistep furin-dependent mechanism. At least part of the final processing event, i.e. cleavage following Arg(220) (mouse sequence annotation), occurs at the cell surface. ADAMTS7B is an active metalloproteinase as shown by its ability to cleave alpha(2)-macroglobulin, but it does not cleave specific peptide bonds in versican and aggrecan attacked by ADAMTS proteases. Together with ADAMTS12, whose primary structure also predicts a mucin domain, ADAMTS7B constitutes a unique subgroup of the ADAMTS family.


A measure for describing and comparing post-reproductive lifespan as a population trait.
1. While-classical life-history theory does not predict post-reproductive lifespan (PRLS), it has been detected in a great number of taxa, leading to the view that it is a broadly conserved trait, and attempts to reconcile theory with these observations. We suggest an alternative: the apparently wide distribution of significant PRLS is an artifact of insufficient methods.2. PRLS is traditionally measured in units of time between each individual's last parturition and death, after excluding those individuals for whom this interval is short. A mean of this measure is then calculated as a population value. We show this traditional population measure (which we denote PrT) to be inconsistently calculated, inherently biased, strongly correlated with overall longevity, uninformative on the importance of PRLS in a population's life-history, unable to use the most-commonly available form of relevant data and without a realistic null hypothesis. Using data altered to ensure that the null hypothesis is true, we find a false positive rate of 0.47 for PrT.3. We propose an alternative population measure, using life-table methods. Post-reproductive Representation (PrR) is the proportion of adult years lived which are post-reproductive. We briefly derive PrR and discuss its properties. We employ a demographic simulation, based on the null hypothesis of simultaneous and proportional decline in survivorship and fecundity, to produce a null distribution for PrR based on the age-specific rates of a population.4. In an example analysis, using data on 84 populations of human and non-human primates, we demonstrate the ability of PrR to represent the effects of artificial protection from mortality and of humanness on PRLS. PrR is found to be higher for all human populations under a wide range of conditions than for any non-human primate in our sample. A strong effect of artificial protection is found, but humans under the most-adverse conditions still achieve PrR of >0.3.5. PrT should not be used as a population measure, and should be used as an individual measure only with great caution. The use of PrR as an intuitive, statistically valid and intercomparable population life-history measure is encouraged.


Stabilization of a raw starch digesting amylase from Aspergillus carbonarius via immobilization on activated and non-activated agarose gel.
Applications of raw starch digesting amylases (RSDAs) are limited due to instability, product inhibition of enzyme and contamination. RSDA from Aspergillus carbonarius was stabilized through immobilization on agarose gel by adsorption, spontaneous crosslinking and conjugation using glycidol, glutaraldehyde or polyglutaraldehyde. Effects of immobilization on kinetics, catalytic, storage and operational stability of immobilized enzyme were evaluated. Polyglutaraldehyde activated agarose RSDA (PGAg-RSDA) gave the highest immobilization yield (100%) with expressed activity of 86.7% while that of glycidol activated RSDA (GlyAg-RSDA) was 80.4%. A shift in pH from optimum of 5 for the soluble enzyme to 6 for RSDA adsorbed on agarose followed by crosslinking with glutaraldehyde (AgRSDA-CROSS) and simultaneous adsorption and crosslinking (AgRSDA-RET), and pH 7 for PGAg-RSDA was seen. PGAg-RSDA and AgRSDA-CROSS were most pH stable and retained over 82% of their activities between pH 3.5 and 9 compared to 59% for the soluble enzyme. Thermoinactivation studies showed that immobilized RSDAs with the exception of GAg-RSDA retained over 90% of their activities at 60°C for 120 min while soluble enzyme retained only 76% activity under the same condition. AgRSDA-CROSS, PGAg-RSDA, Gly-RSDA and GAg-RSDA retained approximately 100% of their activities after 30 days storage at 4°C. GlyAg-RSDA retained 99.6%, PGAg-RSDA 94%, AgRSDA-CROSS 90%, GAg-RSDA 86.5% and Ag-RSDA-RET 80% activity after 10 batch reactions. Immobilization stabilized RSDA and permits processing at higher temperatures to reduce contamination.


MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells.
Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The fetal neural stem cells (NSCs) that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expression in NSCs. To understand the role of miR-153 in the etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo, by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs and gene networks as important miR-153 targets. Moreover, miR-153 over-expression prevented neuronal differentiation without altering neuroepithelial cell survival or proliferation. Analysis of 3'UTRs and in utero over-expression of pre-miR-153 in fetal mouse brain identified Nfia (nuclear factor-1A) and its paralog, Nfib, as direct targets of miR-153. In utero ethanol exposure resulted in a predicted expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR-153 over-expression prevented, and partly reversed, the effects of ethanol exposure on miR-153 target transcripts. Varenicline, a partial nicotinic acetylcholine receptor agonist that, like nicotine, induces miR-153 expression, also prevented and reversed the effects of ethanol exposure. These data collectively provide evidence for a role for miR-153 in preventing premature NSC differentiation. Moreover, they provide the first evidence in a preclinical model that direct or pharmacological manipulation of miRNAs have the potential to prevent or even reverse effects of a teratogen like ethanol on fetal development.


Regeneration of insertionally inactivated streptococcal DNA fragments after excision of transposon Tn916 in Escherichia coli: strategy for targeting and cloning of genes from gram-positive bacteria.
The conjugative transposon Tn916 (15 kilobases), originally identified in Streptococcus faecalis DS16, has been cloned as an intact element on the pBR322-derived vector pGL101 in Escherichia coli. The EcoRI F' (EcoRI F::Tn916) fragment of pAM211 (pAD1::Tn916) was cloned into the single EcoRI site of pGL101 to form the chimera, pAM120, by selecting for the expression of Tn916-encoded tetracycline resistance (Tcr). Interestingly, in the absence of continued selection for Tcr, Tn916 excised from pAM120 at high frequency. This excision event resulted in a plasmid species consisting of the pGL101 vector and a 2.7-kilobase restriction fragment comigrating with the EcoRI F fragment of pAD1 during agarose gel electrophoresis. Filter blot hybridization experiments showed the 2.7-kilobase fragment generated as a result of Tn916 excision to be homologous with the EcoRI F fragment of pAD1. Analogous results were obtained with another chimera, pAM170, generated by ligating the EcoRI D' (EcoRI D::Tn916) fragment of pAM210 (pAD1::Tn916) to EcoRI-digested pGL101. Comparison of the AluI and RsaI cleavage patterns of the EcoRI F fragment isolated after Tn916 excision with those from an EcoRI F fragment derived from pAD1 failed to detect any difference in the two fragments: data in support of a precise Tn916 excision event in E. coli. Subcloning experiments showed that an intact transposon was required for Tn916 excision and located the Tcr determinant near the single HindIII site on Tn916. Although excision occurred with high frequency in E. coli, Tn916 insertion into the E. coli chromosome was a much rarer event. Tcr transformants were not obtained when pAM120 DNA was used to transform a polA1 strain, E. coli C2368.


CD9 inhibition reveals a functional connection of extracellular vesicle secretion with mitophagy in melanoma cells.
Tetraspanins are often used as Extracellular Vesicle (EV) detection markers because of their abundance on these secreted vesicles. However, data on their function on EV biogenesis are controversial and compensatory mechanisms often occur upon gene deletion. To overcome this handicap, we have compared the effects of tetraspanin CD9 gene deletion with those elicited by cytopermeable peptides with blocking properties against tetraspanin CD9. Both CD9 peptide or gene deletion reduced the number of early endosomes. CD9 peptide induced an increase in lysosome numbers, while CD9 deletion augmented the number of MVB and EV secretion, probably because of compensatory CD63 expression upregulation. In vivo, CD9 peptide delayed primary tumour cell growth and reduced metastasis size. These effects on cell proliferation were shown to be concomitant with an impairment in mitochondrial quality control. CD9 KO cells were able to compensate the mitochondrial malfunction by increasing total mitochondrial mass reducing mitophagy. Our data thus provide the first evidence for a functional connection of tetraspanin CD9 with mitophagy in melanoma cells.


The strategic power of saying no.
Susan Bishop started Bishop Partners with the aim of making it the best boutique executive-search firm in the business. Specializing in television, radio, and publishing industries, her plan was to beat out her larger, established competitors through superb execution. Great service would lead to happy clients, which would lead to more business, which would keep clients happy, which would lead to even more business. A virtuous circle, right? Wrong. Before long, she and her staff grew weary of jumping through every hoop their clients could think of--trying to find candidates for lower-level positions in remote locations at below-market rates, for instance. But what could they do? How could they afford to disappoint any customer when they didn't have that many to begin with? In this vivid first-person account, Bishop describes how she and her staff came to an answer that was highly counterintuitive: stop trying to make everyone happy. Focus instead on making the right customers happy. Raise their prices. Limit their searches to high level positions in their field of expertise. Stick to companies big enough to give them repeat business. As hard as it was to define the right clients, it was even harder to say no to the wrong clients. One member of the staff had to turn down work worth $120,000; Bishop herself had to turn down $250,000 from her largest client, Coca-Cola. But in the end, those clients came back with higher-quality work, and her company was on its way from chaotic little start-up to successful, professional enterprise. Bishop tells the classic entrepreneur's story, one with important lessons about strategy making, courage, and discipline for all businesspeople.


Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type diffuse large B-cell lymphoma.
Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focused attention on the changes in GEP accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo patients with DLBCL. COO remained stable from diagnosis to relapse in 80% of patients, with only a single patient showing COO switching from activated B-cell-like (ABC) to germinal center B-cell-like (GCB). Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes that defined clinically distinct high- and low-risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of <60-year-old patients with superior PFS and OS treated with ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials.


Factors Favouring the Development of Clostridium Difficile Infection in Critically Ill Patients.
Clostridium difficile, an anaerobic, spore-forming, toxin-forming, gram-positive bacillus present in the bacterial flora of the colon is the principal cause of nosocomial diarrhoea in adults. Assessment of favouring factors of Clostridium difficile infections as well as the interactions between them, in critically ill hospitalized patients undergoing complex medical and surgical treatments. A retrospective case-control study involving eighty patients admitted in the Intensive Care Unit (ICU) of the County Clinical Emergency Hospital Tîrgu-Mureş was conducted between January and October 2014. Patients aged eighteen years and over, who had undergone complex medical and surgical treatment, were divided into two subgroups. Group 1 included patients who developed diarrhoea but were not diagnosed as having a Clostridium difficile infection (CDI). Group 2 included patients who developed diarrhoea due to CDI as indicated by a positive culture and the expression of exotoxin. The assessed parameters were age, length of stay (LOS), antibiotic spectrum, association with proton pump inhibitors (PPI) or H2-receptor antagonists, immunological status, the presence or lack of gastrointestinal tract surgery. The mean age was 64.6 years with an average LOS of 10 days. Fifty-six percent of patients came to the ICU from internal medicine wards and forty-three percent from surgical wards. 20.5% of them were immunosuppressed. Co-association of ceftriaxone and pantoprazole significantly increased the risk of CDI compared to co-administration of any other antibiotic or pantoprazole (p=0.01). The odds ratio for Pantoprazole together with any antibiotic versus antibiotic therapy alone was significantly higher (p=0.018) with a sevenfold increase in the risk of positive exotoxin increase. Antibiotic use is associated with "no risk to develop CDI" in the first five days of administration. PPIs associated therapy increased the risk of CDI in first seventy-two hours regardless of the antibiotic type, and contributes to an active expression of CD exotoxin.


Acquisition of a bacterial RumA-type tRNA(uracil-54, C5)-methyltransferase by Archaea through an ancient horizontal gene transfer.
The Pyrococcus abyssi genome displays two genes possibly coding for S-adenosyl-l-methionine-dependent RNA(uracil, C5)-methyltransferases (PAB0719 and PAB0760). Their amino acid sequences are more closely related to Escherichia coli RumA catalysing the formation of 5-methyluridine (m(5)U)-1939 in 23S rRNA than to E. coli TrmA (tRNA methyltransferase A) methylating uridine-54 in tRNA. Comparative genomic and phylogenetic analyses show that homologues of PAB0719 and PAB0760 occur only in a few Archaea, these genes having been acquired via a single horizontal gene transfer from a bacterial donor to the common ancestor of Thermococcales and Nanoarchaea. This transfer event was followed by a duplication event in Thermococcales leading to two closely related genes. None of the gene products of the two P. abyssi paralogues catalyses in vitro the formation of m(5)U in a P. abyssi rRNA fragment homologous to the bacterial RumA substrate. Instead, PAB0719 enzyme (renamed (Pab)TrmU54) displays an identical specificity to TrmA, as it catalyses the in vitro formation of m(5)U-54 in tRNA. Thus, during evolution, at least one of the two P. abyssi RumA-type enzymes has changed of target specificity. This functional shift probably occurred in an ancestor of all Thermococcales. This study also provides new evidence in favour of a close relationship between Thermococcales and Nanoarchaea.


Transition metal-catalyzed C-H functionalization of N-oxyenamine internal oxidants.
The transition metal-catalyzed C-H functionalization with hydroxylamine derivatives serving as both reactants and internal oxidants has attracted a lot of interest. These reactions obviate the need for external oxidants and therefore result in high reactivity and selectivity, as well as excellent functional group tolerance under mild reaction conditions, and moreover, water, methanol or carboxylic acid is generally released as the by-product, thus leading to reduced waste. This review focuses on the transition metal-catalyzed oxidative C-H functionalization of N-oxyenamine internal oxidants, with an emphasis on the scope and limitations, as well as the mechanisms of these reactions.


Fatal injuries of US citizens abroad.
US citizens are increasingly traveling, working, and studying abroad as well as retiring abroad. The objective of this study was to describe the type and scope of injury deaths among US citizens abroad and to compare injury death proportions by region to those in the United States. A cross-sectional design using reports of US citizen deaths abroad for 1998, 2000, and 2002 on file at the US State Department was employed. The main outcome measures were the frequencies of injury deaths and proportional mortality ratios (PMRs) comparing deaths abroad to deaths in the United States. Two thousand eleven injury deaths were reported in the 3 years, comprising 13% of all deaths. The overall age-adjusted PMR for injury fatalities abroad compared to the United States was 1.6 (95% confidence interval 1.6-1.7). The highest age-adjusted PMRs for motor vehicle crashes were found in Africa (2.7) and Southeast Asia (1.6). The proportion of drowning deaths was elevated in all regions abroad. Injuries occur at a higher proportion abroad than in the United States. Motor vehicle crash and drowning fatalities are of particular concern. Improved data quality and surveillance of deaths would help government agencies create more evidence-based country advisories.


Combination therapy with interleukin-2 and wild-type p53 expressed by adenoviral vectors potentiates tumor regression in a murine model of breast cancer.
Although cytokine gene transfer for cancer treatment can stimulate immune recognition and tumor regression in animal models, there is still a need for improvements to these strategies. In this study, we examined the efficacy of a combination gene therapy using adenovirus (Ad) 5 vectors expressing human interleukin-2 and the wild-type (wt) human p53 gene under control of the human cytomegalovirus immediate early promoter (AdIL-2 and Adp53wt, respectively). Infected murine cell lines and primary mouse tumor cells secreted high levels of IL-2 and over expressed the p53 protein for at least 9 days. After infection of cells with Adp53wt, DNA synthesis was significantly inhibited and apoptosis was induced within 3-5 days. Both vectors were tested in a transgenic mouse mammary adenocarcinoma model for antitumor response. Following a single intratumoral injection of mice bearing PyMT induced tumors, the combination of Adp53wt (1 x 10(9) pfu) plus a relatively low dose of AdIL-2 (1.5 x 10(8) pfu) caused regressions in 65% of the treated tumors without toxicity. Fifty percent of the treated mice remained tumor free and were immune to rechallenge with fresh tumor cells. In contrast, injection of either vector alone at this does resulted in only a delay in tumor growth. Only mice co-injected with Adp53wt and AdIL-2 showed specific antitumor cytolytic T lymphocyte (CTL) activity, indicating that the immune response involved in tumor regression was promoted by the combination therapy. These results suggest that cancer treatment strategies involving combined delivery of immunomodulatory and antiproliferative genes may be highly effective.


Deep brain stimulation for dystonia.
Within the past few years, there has been a renaissance of functional neurosurgery for the treatment of dystonic movement disorders. In particular, deep brain stimulation (DBS) has widened the spectrum of therapeutical options for patients with otherwise intractable dystonia. It has been introduced only with a delay after DBS became an accepted treatment for advanced Parkinson' disease (PD). In this overview, the authors summarize the current status of its clinical application in dystonia. Deep brain stimulation for dystonia has been developed from radiofrequency lesioning, but it has replaced the latter largely in most centers. The main target used for primary dystonia is the posteroventral globus pallidus internus (GPi), and its efficacy has been shown in generalized dystonia, segmental dystonia, and complex cervical dystonia. The optimal target for secondary dystonias is still unclear, but some patients appear to benefit more from thalamic stimulation. The improvement of dystonia with chronic DBS frequently is delayed, in particular concerning tonic dystonic postures. Because more energy is needed for stimulation than in other movement disorders such as PD, more frequent battery replacements are necessary, which results in relatively higher costs for chronic DBS. The study of intraoperative microelectrode recordings and of local field potentials by the implanted DBS electrodes has yielded new insights in the pathophysiology of dystonia. Larger studies are underway presently to validate the observations being made.


Screening for postpartum depression in an inner-city population.
This study was undertaken to determine the prevalence of positive screens for postpartum depression by using the Edinburgh Postnatal Depression Scale (EPDS) in an inner-city population. At their postpartum visits, women who were seen in two inner-city practices between February 20 and April 30, 2002, self-administered the EPDS. A threshold of 10 or more points was selected as a positive screen for postpartum depression. If the patient responded that she had thoughts of harming herself or others, she was referred immediately for social work or psychiatric evaluation. Otherwise, providers were blinded to the results of the screen. Of the 443 patients who were scheduled for postpartum visits during this time period, 285 (64%) patients presented for their postpartum visit. One hundred twenty-one (42%) of these patients participated in the study and 1 patient did not complete the questionnaire. Twenty-seven (22%) of the 121 patients had a positive screen for postpartum depression. Eight patients (6.6%) reported experiencing suicidal ideation within the previous week. Without use of the screening tool, providers identified 16 (13%) patients who they thought were at risk for postpartum depression. Of those 16 patients, 14 had positive screens on the EPDS. Eight patients eventually had clinical depression diagnosed. There was a significant relationship between women with elevated scores on the EPDS and a personal history of depression (P <.0006), history of prior treatment for depression (P <.0001), and feeling depressed during the pregnancy (P <.0001). Providers failed to comment on the patient's mood in 34 (28%) of the 121 patients. A larger than expected number of women had a positive screen for postpartum depression in our population. This unexpected finding suggests the need for more resources to be directed toward the research, identification, and treatment of postpartum depression in inner-city populations.


The nurse educator and the nursing student: a review of the issue of clinical evaluation procedures.
Research in the area of grievance and appeal mechanisms is very limited. Although writers have addressed aspects of their use, only one study (Orchard, 1991) was carried out to determine what administrative structures and procedures are used to protect both the rights of the instructors and their students in the clinical evaluation process. Further research to both replicate Orchard's study and to analyze specific aspects of nursing programs' existing evaluation and review systems is urgently needed. In the interim, nursing education administrators must rely on this seminal research and/or their personal experiences in the management of failing students. These experiences are augmented by overall institutional policies and reviewed through nursing program accreditation reviews. Although these parameters assist nursing education administrators in determining processes to use when dealing with failing students, they do not guarantee that nursing students or their clinical instructors' rights are protected. Nurse educators need to gain increased knowledge about the legal side of their instructor role (Woodside, 1981). Perhaps once they gain such knowledge, some of the fear frequently experienced by instructors when they are faced with a student threatening to grieve their clinical evaluation will decrease.


Mucous membrane pemphigoid: an update.
To review articles on mucous membrane pemphigoid, published between June 2004-May 2005. Decreased glycosylation of mucin was found in patients with ocular cicatricial pemphigoid. A unique antigen in oral mucous membrane pemphigoid has not yet been identified. Increased vascular cell adhesion molecule and intercellular adhesion molecule 1 expression was found in skin of patients affected by mucous membrane pemphigoid. Autoreactive T cells to an epitope of bullous pemphigoid antigen 180 kilodaltons were identified in the blood of some patients with mucous membrane pemphigoid. Circulating IgA against an antigen in mucous membrane pemphigoid was found in about 20% of patients, without prognostic significance. Enhanced sensitivity for direct immunofluorescence was reported if skin biopsy specimens were stored for 24 hours in saline. An enzyme-linked immunosorbent assay for detection of circulating autoantibodies against laminin-5 was developed. Sensitivity was higher than indirect immunofluorescence on salt-split skin and immunoblotting. Patients with younger onset (<60 years) of ocular cicatricial pemphigoid were found to have disease evolution similar to that of an older group (>70 years) but were visually impaired earlier in life. Intravenous immunoglobulin as treatment of ocular cicatricial pemphigoid was found to be superior to conventional immunosuppressants, with fewer side effects and better long-term outcome for halting disease activity. Intraoperative adjunction of mitomycin C during fornix reconstruction with amniotic membrane resulted in achieving a deeper fornix in 83% of patients with various cicatrizing conjunctivitis. Transplantation of cultured epithelial cells of oral mucosa in corneal limbal stem cell deficiency was successful in improving visual acuity and reestablishing corneal transparency in mid- to advanced ocular cicatricial pemphigoid. Further advances have been achieved in the field of mucous membrane pemphigoid.


Homology Model-Based Virtual Screening for the Identification of Human Helicase DDX3 Inhibitors.
Targeting cellular cofactors instead of viral enzymes represents a new strategy to combat infectious diseases, which should help to overcome the problem of viral resistance. Recently, it has been revealed that the cellular ATPase/RNA helicase X-linked DEAD-box polypeptide 3 (DDX3) is an essential host factor for the replication of several viruses such as HIV, HCV, JEV, Dengue, and West Nile. Accordingly, a drug targeting DDX3 could theoretically inhibit all viruses that are dependent on this host factor. Herein, for the first time, a model of hDDX3 in its closed conformation, which binds the viral RNA was developed by using the homology module of Prime through the Maestro interface of Schrodinger. Next, a structure-based virtual screening protocol was applied to identify DDX3 small molecule inhibitors targeting the RNA binding pocket. As a result, an impressive hit rate of 40% was obtained with the identification of 10 active compounds out of the 25 tested small molecules. The best poses of the active ligands highlighted the crucial residues to be targeted for the inhibition of the helicase activity of DDX3. The obtained results confirm the reliability of the constructed DDX3/RNA model and the proposed computational strategy for investigating novel DDX3 inhibitors.


Symptoms and health complaints and their association with perceived stress at university: survey of students at eleven faculties in Egypt.
This study examined the relationships between perceived stress and a range of self reported symptoms and health complaints in a representative sample of students at one university in Egypt. The data (3,271 students) was collected during the academic year 2009-2010 at eleven faculties at the university of Assiut city, Egypt. A self-administered questionnaire measured health complaints (22 symptoms) and Cohen's Perceived Stress Scale. Socio-demographic and lifestyle data were also collected. Factor analysis generated four groups of health complaints: psychological, circulatory/breathing, gastrointestinal, and pains/aches, and the internal consistency of each group of symptoms was computed using reliability analyses (Cronbach's alpha). Perceived stress was categorized into four levels based on quartiles. Multiple binomial or multinomial logistic regression analyses analysed the relationship between each of the four groups of symptoms and other students' general characteristics adjusted for the effect of all other groups of symptoms. The symptoms most often reported as having occurred sometimes/very often in the last 12 months were fatigue (85.3%), difficulties to concentrate (78.1%), headache (77.9%), and mood swings (74.5%), while nervousness/anxiety (63.2%) and sleep disorder (63.7%) affected many students. Multinominal logistic regression revealed a clear association and a linear trend between increasing level of stress and a higher frequency of psychological symptoms that remained significant after adjustment for other groups of symptoms. There were no associations between perceived stress and circulatory/breathing symptoms, gastrointestinal symptoms, or for pains/aches. Poor health was consistently associated with higher frequency of symptoms across all symptom groups except for gastrointestinal symptoms. Higher health awareness was associated with lower frequency of psychological and circulatory/breathing symptoms but not for the other two symptom groups. Better quality of life was associated with lower frequency of psychological and partly for circulatory/breathing symptoms, but not for the other two symptom groups. There were differences in levels of psychological symptoms and of perceived stress between faculties, where students of Physical Education showed the lowest risk profile regarding both psychological symptoms and perceived stress, while students of Veterinary Medicine showed the highest risk profile. Across all four symptom groups, females had higher ratings of complaints than males. The high prevalence of health complaints especially of psychological and pains/aches type of symptoms raise concern and calls for preventive actions at universities. Comprehensive programmes would be recommended that take the co-occurence of perceived stress and health complaints into account.


Mediterranean Diet Effect: an Italian picture.
The purpose of this study was to evaluate the overall diet quality effects, mainly on antioxidant nutritional status and some cytokines related to the cellular immune response as well as oxidative stress in a healthy Italian population group. An observational study was conducted on 131 healthy free-living subjects. Dietary intake was assessed by dietary diary. Standardised procedures were used to make anthropometric measurements. On blood samples (serum, plasma and whole blood) were evaluated: antioxidant status by vitamin A, vitamin E, carotenoids, vitamin C, uric acid, SH groups, SOD and GPx activities; lipid blood profile by total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides; total antioxidant capacity by FRAP and TRAP; the immune status by TNF-α, and IL-10 cytokines; the levels of malondialdehyde in the erythrocytes as marker of lipid peroxidation. The daily macronutrients intake (g/day) have shown a high lipids consumption and significant differences between the sexes with regard to daily micronutrients intake. On total sample mean Mediterranean Diet Score (MDS) was 4.5 ± 1.6 and no significant differences between the sexes were present. A greater adherence to a Mediterranean dietary pattern increases the circulating plasma levels of carotenoids (lutein plus zeaxanthin, cryptoxanthin, α and β-carotene), vitamin A and vitamin E. The levels of endogenous antioxidants were also improved. We observed higher levels in anti-inflammatory effect cytokines (IL-10) in subjects with MDS ≥ 6, by contrast, subjects with MDS ≤ 3 show higher levels in sense of proinflammatory (TNF α P < 0.05). Lower levels of MDA were associated with MDS > 4. Our data suggest a protective role of vitamin A against chronic inflammatory conditions especially in subjects with the highest adherence to the Mediterranean-type dietary pattern. Mediterranean dietary pattern is associated with significant amelioration of multiple risk factors, including a better cardiovascular risk profile, reduced oxidative stress and modulation of inflammation.


A Multicenter Phase II Study of Gemcitabine, Capecitabine, and Bevacizumab for Locally Advanced or Metastatic Biliary Tract Cancer.
Vascular endothelial growth factor overexpression, seen in 42% to 76% of biliary tract cancers (BTCs), correlates with poor survival. We explored the safety/efficacy and potential biomarkers for bevacizumab in combination with gemcitabine-capecitabine in advanced BTCs. Inoperable stage III/IV BTC patients in our prospective study were given 1000 mg/m of gemcitabine (on days 1, 8), 650 mg/m of capecitabine (on days 1 to 14), and 15 mg/kg of bevacizumab (on day 1) in 21-day cycles. Circulating tumor cells and quality of life were assessed at baseline and before cycle 2 and 3. In total, 50 patients with gallbladder cancer (22%), intrahepatic (58%), and extrahepatic (20%) cholangiocarcinoma, received a median of 8 treatment cycles for median treatment duration of 5.8 months. Common grade 3/4 toxicities were neutropenia (36%), thrombocytopenia (16%), fatigue (20%), infections (14%), and hand-foot syndrome (10%). There were 12 partial response (24%), 24 stable disease (48%) with clinical benefit rate of 72%. Median progression-free survival was 8.1 months (95% confidence interval, 5.3-9.9). Median overall survival was 10.2 months (95% confidence interval, 7.5-13.7). Circulating tumor cells were identified at baseline in 21/46 patients (46%), who had lower median overall survival compared with those without (9.4 vs. 13.7 mo; P=0.29). Patients with quality of life scores greater than the group median by the end of first cycle of treatment had improved survival compared with those who did not (13.3 vs. 9.4 mo; P=0.39). Addition of bevacizumab to gemcitabine/capecitabine did not improve outcome in an unselected group of patients with advanced BTC compared with historical controls. The selective benefit of vascular endothelial growth factor inhibition in BTC remains to be explored.


Prevalence and Predictors of Substance Use Disorders Among HIV Care Enrollees in the United States.
Prior efforts to estimate U.S. prevalence of substance use disorders (SUDs) in HIV care have been undermined by caveats common to single-site trials. The current work reports on a cohort of 10,652 HIV-positive adults linked to care at seven sites, with available patient data including geography, demography, and risk factor indices, and with substance-specific SUDs identified via self-report instruments with validated diagnostic thresholds. Generalized estimating equations also tested patient indices as SUD predictors. Findings were: (1) a 48 % SUD prevalence rate (between-site range of 21-71 %), with 20 % of the sample evidencing polysubstance use disorder; (2) substance-specific SUD rates of 31 % for marijuana, 19 % alcohol, 13 % methamphetamine, 11 % cocaine, and 4 % opiate; and (3) emergence of younger age and male gender as robust SUD predictors. Findings suggest high rates at which SUDs occur among patients at these urban HIV care sites, detail substance-specific SUD rates, and identify at-risk patient subgroups.


A Systematic Review and Meta-analysis of Antibiotic Treatment Duration for Bacteremia Due to Enterobacteriaceae.
The duration of antibiotic therapy for bacteremia due to Enterobacteriaceae is not well defined. We sought to evaluate the clinical outcomes with shorter- versus longer-course treatment. We performed a systematic search of the PubMed and EMBASE databases through May 2018. Studies presenting comparative outcomes between patients receiving antibiotic treatment for ≤10 days ("short-course") and those treated for >10 days ("long-course") were considered eligible. Four retrospective cohort studies and one randomized controlled trial comprising 2,865 patients met the inclusion criteria. The short- and long-course antibiotic treatments did not differ in 30-day all-cause mortality (1,374 patients; risk ratio [RR] = 0.99; 95% confidence interval [CI], 0.69 to 1.43), 90-day all-cause mortality (1,750 patients; RR = 1.16; 95% CI, 0.81 to 1.66), clinical cure (1,080 patients; RR = 1.02; 95% CI, 0.96 to 1.08), or relapse at 90 days (1,750 patients; RR = 1.08; 95% CI, 0.69 to 1.67). In patients with bacteremia due to Enterobacteriaceae, the short- and long-course antibiotic treatments did not differ significantly in terms of clinical outcomes. Further well-designed studies are needed before treatment for 10 days or less is adopted in clinical practice.


Unusual Proton Transfer Kinetics in Water at the Temperature of Maximum Density.
Water exhibits numerous anomalous properties, many of which remain poorly understood. One of its intriguing behaviors is that it exhibits a temperature of maximum density (TMD) at 4 °C. We provide here new experimental evidence for hitherto unknown abrupt changes in proton transfer kinetics at the TMD. In particular, we show that the lifetime of OH^{-} ions has a maximum at this temperature, in contrast to hydronium ions. Furthermore, base-catalyzed proton transfer shows a sharp local minimum at this temperature, and activation energies change abruptly as well. The measured lifetimes agree with earlier theoretical predictions as the temperature approaches the TMD. Similar results are also found for heavy water at its own TMD. These findings point to a high propensity of forming fourfold coordinated OH^{-} solvation complexes at the TMD, underlining the asymmetry between hydroxide and hydronium transport. These results could help to further elucidate the unusual properties of water and related liquids.


Nucleosome dynamics.
In the 30 years since the discovery of the nucleosome, our picture of it has come into sharp focus. The recent high-resolution structures have provided a wealth of insight into the function of the nucleosome, but they are inherently static. Our current knowledge of how nucleosomes can be reconfigured dynamically is at a much earlier stage. Here, recent advances in the understanding of chromatin structure and dynamics are highlighted. The ways in which different modes of nucleosome reconfiguration are likely to influence each other are discussed, and some of the factors likely to regulate the dynamic properties of nucleosomes are considered.